A mixed-function oxidation system comprised fo glucose oxidase, glucose, horseradish peroxidase, O2, and ferredoxin catalyzes the inactivation of Escherichia coli glutamine synthetase (GS). The same system, minus ferredoxin, catalyzes the peroxidation of histidine to yield a carbonyl derivative. The oxidation of histidine is inhibited by either EDTA, catalase, or Mn(II), and leads to the formation of carbonyl derivative. This reaction may therefore be similar to that involved in the inactivation of GS, in which a single histidine residue is oxidized to a carbonyl derivative. It is hoped that a detailed study of the latter process will help to elucidate the mechanism by which key enzymes are inactivated by MFO systems.